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Alzheimer’s May Be Late-Stage Type 2 Diabetes: The Relationship Between Insulin, Amyloid Plaques, And Enzyme Destruction

Diabetes and Alzheimer's are thought to be linked through excess insulin production flooding into the brain, disrupting amyloid plaque removal. Jill A. Brown, CC BY 2.0

Science has known for years that Alzheimer’s disease and type 2 diabetes are connected, but new research from Albany University suggests the mechanism by which the association forms implicates Alzheimer’s as a product of late-stage diabetes, due to the way increased insulin production stops destructive amyloid plaques from getting broken down.

The research team presented its findings, which are still in the preliminary stages, at the annual Society for Neuroscience meeting in San Diego. Through their investigation, the team found that because type 2 diabetes — the most common form of the disease — causes people’s bodies to overproduce insulin, as a result of high blood glucose, the excess insulin trickles into the brain. Once there, it disrupts a key enzyme that normally erases amyloid plaques, a build-up of which scientists have suspected leads to Alzheimer’s. Without this erasure, the plaques accumulate and cognitive decline follows.

"The discovery could explain why people who develop T2 diabetes often show sharp declines in cognitive function, with an estimated 70 percent developing Alzheimer's — far more than in the rest of the population," Ewan McNay, lead researcher of the study, announced at the conference. "People who develop diabetes have to realize this is about more than controlling their weight or diet. It's also the first step on the road to cognitive decline.”

McNay added the study suggests diet plays a much larger role in determining a person’s risk for Alzheimer’s than once thought. Only about 10 percent of diabetics are type 1, a rarer form where insulin deficiency results entirely from immunological malfunctions in the pancreas — where the hormone is produced. Type 2 can be managed, but not cured, through increased physical exercise and modifying one’s diet. Without proper diet management, the low levels of insulin aren’t able to encourage the brain to process enough glucose, thus reducing communication between neurons and resulting in cognitive decline.

McNay and his colleagues fed lab rats a high-fat diet in order to induce type 2 diabetes. Once their bodies reached a diabetic state, the researchers issued the rats memory tests. They found that as the diabetes worsened so too did the rats’ ability to perform their cognitive tests. When the team examined the rats’ brains, they found build-ups of amyloid plaques. These plaques are misfolded proteins that disrupt neurological function, and although scientists agree they play a role in a person developing mental illnesses, the specific mechanisms are still a mystery. The diabetic rats' build-up of amyloid were a result, McNay explained, of a group of enzymes failing to break down the build-up.

"High levels of insulin swamp this enzyme so that it stops breaking down amyloid,” he noted. “The latter then accumulates until it forms toxic clumps that poison brain cells. It's the same amyloid build-up to blame in both diseases – T2 diabetics really do have low-level Alzheimer's.”

In the United States alone, diabetes is the leading cause of kidney failure, nontraumatic lower limb loss, and blindness among adults, according to the Centers for Disease Control and Prevention (CDC). What’s more, between 2005-2008, measures of glucose post-fasting showed hemoglobin levels indicative of prediabetes in 35 percent of adults. Among those 65 years or older, the rate jumped to 50 percent. The CDC estimates that by those measures, roughly 79 million Americans 20 years and older can be classified as prediabetic.

“People who develop diabetes have to realize this is about more than controlling their weight or diet. It’s also the first step on the road to cognitive decline,” McNay told the Daily Mail. “At first they won’t be able to keep up with their kids playing games, but in 30 years’ time they may not even recognize them.”